The mechanism of the dissociation of renin and aldosterone in hypoxemic states has not been identified. Recent work has suggested that the decrease in aldosterone during hypoxia is due to a direct inhibitory effect of low oxygen on the zona glomerulosa. The long term goal of this project is to determine the sensitivity and mechanism of the effect of oxygen on aldosterone synthesis and secretion. The present study will determine (a) the effect of a full range of PO2 levels (50-450 torr) on aldosterone secretion, (b) the interaction of O2 with CO2 and pH, and (c) the role of 18-hydroxylase in O2-sensitive aldoeteronotenesis. Acutely dispersed bovine zona glomerulosa and fasciculata cells will be incubated at 37 degrees under metal tents through which different gas mixtures are vented. In this way, basal as well as angiotensin and cAMP-stimulated aldosterone and cortisol secretion will be measured under different levels of O2, CO2, and pH. In addition, the effect of oxygen on 18-hydroxylase activity will be determined by measuring the conversion of corticosterone to aldosterone. This work will determine if physiological changes in oxygen directly, specifically and reversibly alter aldosteronogenesis in a O2-level dependent manner and/or by inhibition of 18-hydroxylase activity. Patients with hypoxemia often exhibit fluid and electrolyte disorders possibly in part because they do not exhibit a normal suppression of aldosterone secretion. This may be due to concomitant hypercapnia. Conversely, O2 therapy may be beneficial in the treatment of transient hyperreninemic hypoaldosteronism. Since the penultimate task of the cardiovascular system is the delivery of oxygen to the tissues, the role of oxygen and its delivery in the control of aldosterone is of fundamental basic and clinical importance.
